This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The molecular mechanism of general anesthesia remains an mystery. Although a superfamily of pentameric ligand gated ion channels (pLGICs) has been identified as potential targets of general anesthetics, the lack of high-resolution structures of these pLGICs hinders the understanding where anesthetic binding sites are in these proteins and how anesthetic bindings impact on protein functions. An exciting platform for getting the answers has recently emerged as the x-ray structures of two bacterial homologs to the pLGIC family, GLIC and ELIC, were solved. As cation channels, GLIC and ELIC can be crystallized in the open- and close-channel states, respectively. Similar to mammalian pLGIC cation channels, cation conductance of GLIC could be inhibited by a variety of anesthetics at subclinical doses. Here we propose to co-crystallize GLIC and ELIC with general anesthetics. No anesthetic has been crystallized with any pLGICs in the past. The x-ray structures of GLIC- and ELIC-anesthetics complexes will provide novel structural basis to explain the functional impact of general anesthetics to the pLGICs. Inhaled anesthetic halothane and intravenous anesthetics thiopental and ketamine are chosen for the study.